GENOMIC INSTABILITY

基因组不稳定

• 批准号: 5200345
• 负责人: V A BOHR
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5200345
• 关键词: DNA damage; DNA repair; aging; colorectal neoplasms; neoplasm /cancer genetics; telomere; tissue /cell culture; tumor suppressor genes

Genomic instability is a general and characteristic feature of both cancer and aging. We are searching for the underlying mechanisms that are responsible for the development of the genomic instability. Replication errors in DNA, telomeric shortening, increased local DNA damage formation, and localized DNA repair defects, are all possible pathways that can lead to genomic instability. Recently, we have found situations where the genomic instability correlated with a deficiency in DNA repair. We are now examining these pathways in human cells from patients with aging or cancer associated genomic instabilities. a good example is hereditary, non-polyposis colorectal carcinoma (HNPCC), where a mismatch DNA repair defect has been found. We find a more generalized DNA repair defect. This will be further characterized and explored in other HNPCC cell lines. In other studies, we find a distinct shortening of the telomeres in cell lines that have mutations or are deficient in the function of the tumorsupressor gene, p53, which then leads to genomic instability.

基因组的不稳定性是这两种疾病的普遍特征 癌症和衰老。我们正在寻找潜在的机制， 对基因组不稳定性的发展负有责任。 DNA复制错误、端粒缩短、局部DNA增加 损伤的形成和局部的DNA修复缺陷都是可能的 可能导致基因组不稳定的途径。最近，我们发现 基因组不稳定与基因缺陷相关的情况 DNA修复。我们现在正在研究人类细胞中的这些通路 与衰老或癌症相关的基因组不稳定的患者。A好的 例如遗传性非息肉病性结直肠癌(HNPCC)，其中 发现了一个错配的DNA修复缺陷。我们发现了一个更普遍的 DNA修复缺陷。这将在中进一步描述和探索 其他HNPCC细胞株。在其他研究中，我们发现了一个明显的缩写 在有突变或基因缺陷的细胞系中的端粒 肿瘤抑制基因P53的功能，然后导致基因组 不稳定。